Neural Deterioration and Cross-modal Plasticity in the Blind

Ione Fine, Ph.D.

Funded in June, 2006: $100000 for 3 years

Using Imaging to Learn How to Maximally Restore Visual Functioning

Using MRI and fMRI in people who are blind at an early age and those who became blind later in life, the researchers will study how visual deprivation affects the visual cortex and how brain plasticity affects the cortex’s responses to non-visual senses. The results may improve approaches for restoring visual function following use of emerging therapeutic advances, such as corneal and retinal transplants, gene therapy, and retinal prostheses.

Animal model research has shown that when sensory deprivation (such as blindness) occurs early, rather than later in life, there is a greater disruption of neuronal organization. Additionally, when the sensory cortex is deprived early in life, it is more responsive to other senses, according to both animal and human studies. This adaptive process is called “cross-modal” plasticity. The researchers will determine how neuronal deterioration caused by losing vision is related to this cross-modal plasticity. They will use MRS to identify biomarkers of neuronal deterioration in healthy participants and in people who were blind early compared to those who became blind in adulthood. Then the researchers will use fMRI in the three participant groups to measure neural activity in response to auditory and tactile stimuli within the visual cortex.

The investigators hypothesize that cross-modal plasticity may provide an alternative form of sensory input that helps to prevent neural deterioration in the absence of vision. If this is the case, they will find less neuronal deterioration in patients who were blind early, and for a longer time, than people who became blind in adulthood.

Significance: If this research shows that early cross-modal plasticity helps to spare neuronal degeneration, parents of blind children may be more willing to encourage their children to read Braille and use a cane. Moreover, this use of other sensory modalities to help preserve neurons in the visual cortex in turn may help improve the outcomes of evolving therapies, such as corneal and retinal transplants.

Neural Deterioration and Cross-modal Plasticity in the Blind

Numerous brain-imaging studies have found responses to tactile and auditory stimuli in the visual cortex of blind subjects. It seems that losing a sense early in life leads to a sensory reorganization whereby visual cortex (if sight is restored), shows a deterioration in processing visual information, and begins to process information from other senses. This cross-modal plasticity is thought to play an important role in helping blind subjects perform well on complex tactile and auditory tasks, such as reading Braille and orienting themselves using the sound of a tapping cane. We propose:

(1) To measure changes in brain metabolites in early visual cortex as a result of visual deprivation.
(2) To test whether cross-modal plasticity may maintain neuronal function (and connectivity) within cortical areas that would otherwise be silent and susceptible to neural degeneration.

Hypothesis:
Cross-modal plasticity may help to prevent neural deterioration in visual areas as a result of blindness. According to this hypothesis, we should find less neuronal deterioration in patients who are deprived of vision early in life and have strong cross-modal responses in deprived brain regions.

Goals:
We will assess neural deterioration using magnetic resonance spectroscopy to measure the quantities of molecules associated with a variety of neuronal structures in the human brain. We will measure cross-modal plasticity in the same subjects using functional magnetic resonance imaging to measure neural activity in response to auditory and tactile stimuli within brain regions normally associated with vision. We will compare responses across adults who became blind early in life, adults who became blind in adulthood, and visually normal adults.

Methods:We will use three groups of age-matched subjects: early-blind, late-blind, and visually normal controls.

Functional Magnetic Resonance Imaging will be used to measure cross-modal responses in visual cortex for two tactile discrimination tasks (offset discrimination and Braille reading) and one auditory task (tone localization) in these same subjects. Tasks will be based on previous studies of cross-modal plasticity in the blind.

Proton MRS will be used to measure the concentrations of brain metabolites such creatine (associated with myelination and gial cells), NAA (a marker for neuronal density), lactate (a marker of anaerobic metabolism), glutamate, glutamine, and GABA (the development of the GABA pathway is heavily disrupted by dark rearing) within the visual cortex.

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